The objective of this proposal is to develop techniques for the analysis of the DNA structure of human chromosome 11. The experimental approach involves the comparison of maps of the chromosome derived by three different approaches. 1. Genetic linkage among sites on the chromosome defined by restriction fragment length polymorphisms. 2. Physical association of specific DNA segments in somatic cell hybrids carrying limited regions of the chromosome derived either by selection of hybrids carrying the entire chromosome or by metaphase chromosome transfer. 3. Karyotypic analysis and in situ hybridization of cloned DNA segments to extend metaphase chromosomes. The immediate objectives of the proposal are: 1. To compare genetic map distance to physical distance in nucleotides in a specific region of the chromosome. 2. To isolate DNA segments which cover a contiguous region of several million base pairs of the chromosome. 3. To further develop methods utilizing interspersed repeated DNA sequences as probes to map specific regions of the chromosome. 4. To further develop isolated metaphase chromosome transfer as a tool for mapping regions of the chromosome.